title: Dexamethasone preconditioning improves the response of collagen-induced arthritis to treatment with short-term lipopolysaccharide-stimulated collagen-loaded dendritic cells.
abstract: Background. Pharmacologically modulated dendritic cells (DCs) have been shown to restore tolerance in type II collagen-(CII-) induced arthritis (CIA). We examined the effect of dexamethasone (DXM) administration as a preconditioning agent, followed by an injection of lipopolysaccharide-(LPS-) stimulated and CII-loaded DCs on the CIA course. Methods. After CIA induction, mice pretreated with DXM were injected with 4-hour LPS-stimulated DCs loaded with CII (DXM/4hLPS/CII/DCs). Results. Mice injected with DXM/4hLPS/CII/DCs displayed significantly less severe clinical disease compared to animals receiving 4hLPS/CII/DCs alone or those in which only DXM was administered. Cytokine profile evaluation showed that CD4+ T cells from DXM/4hLPS/CII/DCs and 4hLPS/CII/DCs groups release higher IL-10 levels than those from mice receiving DXM alone or CIA mice. CD4+ T cells from all DC-treated groups showed less IL-17 release when compared to the CIA group. On the contrary, CD4+ T cells from DXM/4hLPS/CII/DCs and 4hLPS/CII/DCs groups released higher IFN- γ levels than those from CIA group. Conclusion. A combined treatment, including DXM preconditioning followed by an inoculation of short-term LPS-stimulated CII-loaded DCs, provides an improved strategy for attenuating CIA severity. Our results suggest that this benefit is driven by a modulation in the cytokine profile secreted by CD4+ T cells.
authors.affiliation: Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Corina
authors.initials: C
authors.lastname: Peña
authors.forename: David
authors.initials: D
authors.lastname: Gárate
authors.forename: Juan
authors.initials: J
authors.lastname: Contreras-Levicoy
authors.forename: Octavio
authors.initials: O
authors.lastname: Aravena
authors.forename: Diego
authors.initials: D
authors.lastname: Catalán
authors.forename: Juan C
authors.initials: JC
authors.lastname: Aguillón
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D024043:Collagen Type II / Q000494:pharmacology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D003907:Dexamethasone / Q000494:pharmacology*; D054796:Drug Dosage Calculations; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008811:Mice, Inbred DBA
chemical_list: D000893:Anti-Inflammatory Agents; D024043:Collagen Type II; D020381:Interleukin-17; D008070:Lipopolysaccharides; D016753:Interleukin-10; D003907:Dexamethasone; D007371:Interferon-gamma